Advance programmed sample processing system and methods of biological slide processing

ABSTRACT

A sample processing system ( 101 ) that may be automated and methods are disclosed where sample(s) ( 198 ) are arranged on a carrier element ( 197 ) and a process operation control system ( 171 ) automatically processes the sample(s) perhaps robotically with a sample process parameter input ( 173 ) that may be independent and an independent process parameter memory that does not interrupt process operation when being used. There may be an interspersial robotic control element responsive to an automatic data replication memory and to which a robotic motion system is responsive.

TECHNICAL FIELD

This application relates to the field of sample processing systems andmethods of entering information for the processing of samples. Thepresent invention may be directed to the automated processing,treatment, or even staining of samples arranged on carriers, such asslides, and in some embodiments, directed to the continuous or batchprocessing of samples and carriers. Embodiments may further relate tocontrol systems for sample processing and data input, acquisition,maintenance, and retrieval for sample processing. Applications to whichthe present invention may especially relate includeimmunohistochemistry, in-situ hybridization, fluorescent in-situhybridization, special staining, and cytology, as well as potentiallyother chemical and biological applications.

BACKGROUND

Sample processing in immunohistochemical (IHC) applications and in otherchemical and biological analyses may require one or a number of variousprocessing sequences or protocols as part of an analysis of one or moresamples. The sample, processing sequences or protocols may be defined bythe individual or organization requesting an analysis, such as apathologist or histologist of a hospital, and may be further defined bythe dictates of a particular analysis to be performed.

In preparation for sample analysis, a biological sample may be acquiredby known sample acquisition techniques and may comprise, for example inIHC applications, tissues generally or even in some applications one ora plurality of isolated cells, such as in microarray samples, and may bepresented on a sample carrier including but not limited to microscopeslides. Furthermore, the sample may be presented on the carriervariously and potentially in some form of preservation. As one example,a sample such as a layer or slice of skin may be preserved informaldehyde and presented on a carrier with one or more paraffin orother chemical layers infiltrating the sample.

Immunologic applications, for example, may require processing sequencesor protocols that comprise steps such as deparaffinization, targetretrieval, reagent application, and staining, especially for in-situhybridization (ISH) techniques. In some applications, these steps mayhave been performed manually, potentially creating a time-intensiveprotocol and necessitating personnel to be actively involved in thesample processing. Even when performed automatically, there have beeninefficiencies in such systems. Attempts have been made to automatesample processing to address the need for expedient sample processingand a less manually burdensome operation. However, such previous effortsmay have not fully addressed certain specific needs for an automatedsample processing system. Previous efforts to automate sample processingmay be deficient in several aspects that prevent more robust automatedsample processing, such as: the lack of sufficient computer control andmonitoring of sample processing; the lack of information sharing forprocessing protocol and processing status, especially for individualsamples; the lack of practical information input and process definitionentry capabilities; the lack of diagnostic capabilities; and the lack ofreal-time or adaptive capabilities for multiple sample batch processing.

Past efforts at automated sample processing for samples presented oncarriers such as slides, such as U.S. Pat. No. 6,352,861 to VentanaMedical Systems, Inc. and U.S. Pat. No. 5,839,091 to LabVisionCorporation, have not afforded the various advantages and othercombinations of features as presented herein.

One of the various aspects that has not been adequately addressed ineven automated process system is that of information entry. In practicalterms, entry has often required both detailed knowledge of anoften-sophisticated process system and physical access to such systems.It has also been frequently limited to entry or input of data at orabout the time the actual processing was to occur. In spite of the factthat many have appreciated the practical needs of users and institutionsin this regard, such aspects have not been an adequately address todate.

DISCLOSURE OF INVETION

The present invention presents an automated sample processing systemthat greatly simplifies and make extremely more practical the functionsof inputting information for automated sample processing. As described,sample processing can be accomplished as disclosed herein. In providingthis disclosure, it should be understood that the various examples anddesigns disclosed for sample processing and other disclosed techniques,are not meant to limit the present invention to any particularembodiment, whether apparatus, method, or otherwise. These descriptionsare provided rather to describe various sample processing techniques ina manner in which the present invention can be understood. Thedescriptions incorporated by reference and the various examples shouldnot be construed to limit the present invention to only such techniques.This disclosure, however, may be understood to incorporate the varioustechniques in the context of the various embodiments of the presentinvention.

The techniques and systems of sample processing are addressed in afashion that may provide the processing of one or more samples or of aplurality of groups of one or more samples in sequential ornon-sequential fashion. Processing of samples may be determined by theprotocol to be followed for each sample or a protocol for multiplesamples. Aspects of the present invention may be especially applicableto sample processing having one or a plurality of processing steps to beperformed on one, a portion, or an entirety of samples, such protocolsidentified in some instances by individual carriers presenting thesamples or by the individual samples themselves. As mentioned, thepresent invention may be especially applicable to immunohistochemistry(IHC) techniques, as well as in-situ hybridization (ISH) and fluorescentin-situ hybridization (FISH), special staining of samples, andmicroarrays; especially techniques incorporating target retrieval or thestaining of samples. Furthermore, embodiments may be directed toprocessing sequences addressing issues of processing control.

Embodiments of the invention may further relate to automated controlsystems for sample processing. Embodiments may also be directed to dataacquisition, input, maintenance, and retrieval for sample processing, aswell as information sharing of processing protocol and processinginformation, and real-time or adaptive capabilities for processing.

To disclose the foregoing and other objects and in accordance with thepurposes of the present invention, as broadly embodied and describedherein, the present invention is characterized in various claims and inexplanatory disclosure. None of these should be understood as limiting.Further, all claims presented at any time are incorporated in thespecification to afford all opportunities of presentation. Claimspotentially to be pursued for some of the initially presented aspects ofthe invention may include any aspects described.

To achieve the foregoing and other objects of invention, and as may befurther disclosed and claimed throughout this description, the inventionmay comprise an automated sample processing system comprising aplurality of drawers, a plurality of sample carrier elements that mayeven be each removably configured with one of the drawers, and anadaptive or other sample processing control system. The sample carriersmay be both movable and removable. The sample processing control systemmay automate the sample processing system such that one or more samplesmay be processed according to one or more protocols, potentiallyindicated by information on slides or otherwise input to the system.This sample processing may comprise one or more sampling protocols andsteps, such as deparaffinization, target retrieval, and staining.

A sensor may be provided in some embodiments that may automaticallyidentify information from one or more samples, sample carriers, orslides. In embodiments, protocol information may be provided or madeavailable by the sample processing control system. The sample processingsystem may then process one or more samples or perhaps slides, or one ormore batches of slides, concurrently, sequentially, or in any othertemporal fashion, potentially in accordance with protocol informationpreviously provided for a sample by a user or other decision maker. Thisinformation can then be made available for use by the sample processingcontrol system. Sample batches or individual slides may even be insertedor removed during processing protocol steps by the control andmonitoring accomplished by the adaptive sample processing controlsystem.

Another embodiment of the present invention that may achieve theforegoing and other objects of invention may comprise a method of sampleprocessing, comprising the steps of: accessing at least one of aplurality of samples or sample drawers, providing at least one samplecarrier or perhaps a sample carrier retainment assembly configured withat least one sample, configuring at least one of the drawers with the atleast one sample carrier, and adaptively processing the sample. The stepof processing or perhaps even adaptive processing may be applied toautomate the processing of samples and may allow for either or bothcontinuous or batch processing of samples or slides. It may also affordmultiple independent sample or slide processing and in some embodimentsslide processing to process each slide independently.

Embodiments of the invention may further comprise a method of automatedsample processing, comprising the steps of: acquiring or accepting oraccessing information such as protocol information, transmitting suchinformation to at least one sample processing system or even a standalone processing system, and processing samples. Furthermore,embodiments may provide: for handling, maintaining, sharing, and usingthe sample processing information. These and other aspects may beprovided for individual samples or multiple batch processing, and in areal-time manner. It may also be accomplished in and adaptive manner,perhaps for multiple batch processing or the like.

Again, as mentioned, many of the various aspects of the presentinvention are applicable to immunohistochemistry (IHC), as well asin-situ hybridization (ISH) and fluorescent in-situ hybridization(FISH), special staining of samples, microarray processes, andtechniques incorporating target retrieval or the staining of samples.Furthermore, embodiments are directed to processing sequences addressingissues of processing control, and may be particularly applied to slideprocessing systems.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying figures, are incorporated in and form a part of thedescription, illustrate some of the preferred embodiments of the presentinvention. Together with the written description and disclosures of thespecification, they serve to explain principles of the invention and toenable each of the disclosed embodiments.

FIG. 1 is a depiction of an embodiment of an overall systemincorporating some of the features of the invention.

FIG. 2 is a depiction of an embodiment of a portion of a sample carrierassembly of one embodiment of the invention.

FIG. 3 is a depiction of an embodiment of a robotic movement aspect ofone embodiment of the invention.

FIG. 4 is a flow chart of some representative process steps of anembodiment of the invention.

FIG. 5 is a block diagram of an embodiment of the invention.

FIG. 6 is a depiction of an embodiment of a device incorporating some ofthe features of the invention.

FIG. 7 is a depiction of an embodiment connecting one stainer with onemanager & database and one label printer.

FIG. 8 is a depiction of an embodiment connecting multiple stainers withmultiple managers and multiple label printers.

FIG. 9 is a depiction of an embodiment connecting a system to a labnetwork and lab information system.

FIG. 10 is a block diagram showing some of the internal softwarefeatures.

BEST MODES FOR CARRYING OUT THE INVENTION

The following descriptions are provided to describe various embodimentsof the present invention in a manner to facilitate a more detailedunderstanding some of the inventive features. The variously describedexamples and preferred embodiments should not be construed to limit thepresent invention to only the explicitly described systems, techniques,and applications. This description may further be understood toincorporate the various systems, techniques, and applications, bothsingularly and in various combinations consistent with the variousinventive features and embodiments of the present invention.Accordingly, the following is a detailed description of a number ofspecific embodiments of the invention.

FIG. 1 shows one embodiment of a sample processing system 101 inaccordance with the present invention. The sample processing system 101is configured to achieve an appropriate sequence of events that achievesa desires result to some degree. In achieving this sequence in anautomated fashion to some degree the sample processing system is deemedan automated sample processing system and achieves automatic processingof at least one sample. This automated sequence may be controlled byhardware, software, or some combination of them to accomplish a desiredsequence with limited human intervention. Regardless how achieved, theautomated control is provided by a process operation control system 171to direct the various activities. As shown in FIG. 10, this (as well asother functionalities discussed) may be software programming orsubroutines; again, it may also include hardware or the like. The sample198 processed may be any material, but is most likely a biologicmaterial such as a biological sample or a biological specimen, perhapssuch as a histological sample, e.g. tissue and cell specimens, cells,collections of cells, or tissue samples, the definition to include celllines, proteins and synthetic peptides, tissues, cell preps, cellpreparations, blood, bodily fluids, bone marrow, cytology specimens,blood smears, thin-layer preparations, and micro arrays. It should alsobe understood to include slide-based biological samples. As used, asample may be arranged on a carrier element 197 such as a slide or thelike that may maintain the sample's position or integrity. The carrierelement 197 may be configured to move and thus reposition the sample198. As such, it may be considered a movable carrier element. Inprocessing a slide, the automated sample processing system may serve asan automated slide processing system.

A particular design may include cabinet sections 102 that may form outerportions of the system and serve to address general structuralconsiderations of the system (a top cabinet section is not shown in FIG.1). The sample processing system may also comprise a plurality ofdrawers 104 used for the handling and processing of samples and samplecarriers such as slides, potentially microscope slides. Other samplecarriers may be accommodated consistent with the present invention. Eachdrawer may be configured to accommodate carrier retainment assembliesthat hold one or, most likely, a number of the particular carriers,slides, or samples involved.

In holding slides the carrier retainment assembly serves as a slideretainment assembly 106. There may also be carrier racks, modules, ormagazines encompassed within each of the two broad terms. As oneembodiment of a sample carrier retainment assembly, a slide retainmentassembly 106 is shown in FIG. 2. The slide retainment assembly, andindeed the generic carrier retainment assembly may comprise a sliderack, module, or a number of magazines. The slide retainment assembly106 may be configured to accommodate a plurality of slides in at leastone configuration in corresponding sample carrier retention devices 108.The sample carrier retainment assemblies, are utilized in the processingof samples as further described below. It should be further noted thatthe sample carrier retainment assembly can be removably configured withthe drawers 104, and may be stackable or nested within other retainmentassemblies.

The general sample processing system 101, and even one or more drawers110 in the sample processing system 101 may accommodate processingmaterials such as reagent containers 199 for sample processing, alsofurther described-below. A processing material retainment assembly, suchas a container rack 111, shown in FIG. 1, may be utilized to accommodatereagent containers 199 or other processing materials within each ofdrawers 110. Bottle inserts may be preferably configured with theretainment assembly to ensure proper processing material positioningwithin the processing material retainment assembly and the drawer.

Multiple drawers 104 may be included to allow for one or a plurality ofsample processing protocols to be performed by the system 101. Pastefforts at sample processing, as previously described, may have beenlimited to processing sequences for an entire batch of carriers withinthe system. The present invention, however, in part by providing aplurality of drawers and carrier retainment assemblies, may allow forindividual, batch, or multiple batch processing, including real-time oradaptive capabilities, as further described below.

Indicator elements 112 may be provided to indicate a status of thedrawers and the carriers or materials within each drawer for an operatorof the system. In one embodiment, visual indicators, such as lightemitting diodes in preferred embodiments, may be used to indicate if adrawer is available during operation of the sample processing system,and may indicate conditions such as a locked or open condition of acorresponding drawer, carrier capacity status of the drawer or of acarrier retainment assembly within the drawer, and chemical status ofthe sample processing system, such as reagent loading status orcapacity. A warning indication may be given by these or other indicatorelements, as well as other indicative signals. One or a plurality ofsensors may be utilized to determine the status of the drawer asindicated by the indicator elements 112 and to further provideprocessing status as further described below.

A processing material unit may be utilized to provide various processingmaterial to the sample processing system 101 and to afford thesegregation of waste produced during sample processing and the avoidanceof cross-contamination. In one embodiment of the present invention, theprocessing material unit may be configured to accommodate one or aplurality of containers such as deparaffin solution or other materialutilized in sample processing. In some embodiments, the unit may alsoaccommodate waste containers to provide for the collection of wastematerial from the sample processing. Tubing or other fluid transmissionelements may be connected with the containers and the sample processingsystem 101. Tubing or other fluid transmission elements may also beconnected with the waste containers and the system 101.

In accordance with the desire for an automated processing system,embodiments of the present invention may include robotic sample processfunctions or a robotic motion system 172 responsive to the processoperation control system 171 to achieve the desired operation steps.This may further comprise an arm 120 utilized in sample processing,potentially having robotic movement, and in some embodiments, Cartesianmovement. The arm 120 may comprise, in some preferred embodiments, oneor more elements, such as an actuator probe 122, a syringe or probe 124,a sensor element and a non-discrete or other volume fluid and/or airapplicator. The actuator probe may be utilized in the configuration andmanipulation of the carriers in sample processing, further describedbelow. In some preferred embodiments, the actuator probe 122 configuresand manipulates the configuration of slides in the sample carrierretention devices 108 by actuation of carrier adjustment element 130(see for example FIG. 2), and in some embodiments, by contact with theslides. As mentioned, in some embodiments, manipulation or movement ofthe slides or the samples may be accommodated. This movement may resultin a horizontal or vertical configuration of the slides to facilitatesample processing as described below.

As previously mentioned, arm 120 may comprise syringe 124. The syringe124 may be considered a probe in some embodiments, depending upon therequirements of protocols to be performed. Syringe 124 may befluidically connected with and may apply one or more of the following:rinse agents, such as water; containers, potentially removablyfluidically connected for the aspiration of reagents, such as aspirationof reagents from containers and to the samples presented with thecarriers; and blow off or other removal agents such as an air source.Syringe 124 may be utilized to pierce processing material containerssuch as reagent containers. In some embodiments, a reservoir may beprovided with the arm 120 to allow for various volumes to be aspiratedby the syringe 124. The unique configuration of the reservoir allows forefficient cleaning and drying of the internal portions of the syringewhile allowing for the accurate pipetting or otherwise aspiration of awide range of volumes.

Arm 120 may, in some preferred embodiments, comprise a sensor elementThe sensor element may be used to automatically determine location andother status information of components of the sample processing system,such as reagent containers, or other processing material containers, orsample carriers. This may be used to teach the system proper and/oractual locations, and to calibrate, self-calibrate, or self-align thesystem, or the like.

In preferred embodiments, the sample processing system 101 may includean automatic slide identification element. This may be controlled toachieve the act of automatically identifying said plurality of slides.This may also be more generic such as there may be some type of sensorelement and it may even comprise a reader or scanner, such as a CCDcamera, utilized to determine status information of processingmaterials, such as reagents as well as to identify slides. The sensorelement, for example, may read, detect, or otherwise determineinformation in the sample processing system 101, for example, fromprocessing material containers, such as, for example, reading a codeprovided on the container to determine reagent type and reagent locationwithin the system. The sensor element may also determine statusinformation of sample carriers. For example, in some embodiments, slidesconfigured with a slide retainment assembly may be provided withinformational indicia, such as a code, that may indicate informationabout the sample presented on the slide or the processing protocol to beperformed. The sensor element may read the code of the slide todetermine the protocol to be performed for the particular slide andsample.

A cleaning station 140, shown in FIG. 1, may be included to clean one ormore elements of arm 120, and in preferred embodiments, may function toclean or otherwise sterilize syringe 124. In one embodiment, thecleaning station 140 may be configured to allow a drop off and pick upof elements such as syringes for cleaning while allowing the processingthroughput of the sample processing system to continue. The syringe maybe sterilized, for example, with a water rinse through the syringe whilethe syringe is positioned at the cleaning station. In other embodimentsof the present invention, the cleaning station may be configured toclean or otherwise sterilize elements of arm 120, such as syringe 124,while such elements are configured with arm 120.

In some embodiments, multiple probes or syringes may be used to applyfluids required for the staining of histological tissues samples mountedor otherwise presented on slides. This may encompass automatic stainingaccomplished through a slide stain element such as the items included onthe robotic motion system 172 discussed above. The sample processingsystem may drop off a “dirty”, contaminated, or used probe or syringeand swap it for a “clean”, uncontaminated, sterilized or an unused one.One or more probes or syringes may be cleaned while the system continuesprocessing of samples, such as applying reagent or stain with analternate probe or syringe.

The system may access, use and wash multiple probes or syringes forpipetting or otherwise aspirating fluids required for the staining ofsamples mounted or otherwise presented on slides. To eliminate crosscontamination, a system with a single reusable probe may wash the probebetween each fluid applied. The task of washing the probe can have alarge impact on the throughput of the overall system. The presentinvention may allow for multiple probes to be available to the systemfor use. The system may continuously have a clean, uncontaminated,sterilized, or an unused probe available to use and sample processing isnot impacted by the required cleaning routine. The cleaning routine maybe necessary to eliminate the possible cross contamination of fluidsand, in some embodiments, may take up to about 1 minute to accomplish.The cumulative impact of the cleaning routine on a series of processingsteps can add time to the throughput capabilities of the system. Theaddition of multiple probes or syringes may eliminate this impact andsignificantly decreases the time required to process the samples.

Embodiments of the present invention may comprise a mixing station 150,shown in FIG. 1. The system may mix component fluids, such as dyes,buffers, or other processing materials, preferably on demand and as theprocessing steps and protocols dictate. Fluids required during theprocessing steps may sometimes need to be mixed with other fluids tocreate a final activated fluid. However, the activity levels of thesemixtures can be time sensitive and may therefore only be effective for ashort period of time. The on demand mixing of fluids is advantageous inthat it allows the fluids to be mixed immediately before being used. Thesyringe or probe 124, in preferred embodiments, will aspirate fluidsinto and from the mixing station 150 to mix component fluids. A rinsemay further be dispensed into the mixing station to sterilize thestation.

In preferred embodiments, slides are movable and configurable in bothvertical and horizontal positions as required for the pretreatment andstaining process. This allows for the automation of the pretreatment andstaining of slides in various manners, including pretreatment andstaining as accepted in conventional manual laboratory methods. Theslides are initially loaded into the carrier retention assemblies, suchas slide racks, and drawers in the horizontal position. If pretreatmentis required, such as deparaffinization, the system rotates the slideinto the vertical position and lowers these samples into a processingtank, further described below, filled with the required fluids. In someembodiments, the slide rack is lowered to affect lowering of the slides(see FIG. 2). To perform the staining process on the slides, asdescribed below, the System rotates or moves the slide to the horizontalposition and a syringe or probe applies fluid to the sample, providing ahorizontal staining of the sample. Each slide can be rotatedindependently allowing for the independent processing of differentsamples with different requirements.

The system automates, and in some embodiments mimics or otherwisecorresponds to the procedure and physical attributes of the suppliesused manually to perform these same pre-treatment processes.Accordingly, a processing tank may be provided. In some embodiments,components of each processing tank may be configured within a drawer104. In some preferred embodiments, the fluids volume needed to performpre-treatment processes are maintained but instead of the slideorientation with each other being face-to-face, as in conventionalsystems, they are side-to-side, although other slide configurations arenot disclaimed. The processing tanks provide even distribution of fluidsacross the face of the slide.

In some embodiments, the processing tanks have the ability to heat theslides. Heat may also be applied to each individual slide by a thermaldevice. The precision and physical application of the heat can result instandardization and repeatability of process steps. Filling and heatingtasks are performed by a computer controlled scheduler, as furtherdescribed below. Fluid volume may be adjusted to account for thepresence or absence of any number of slides.

In some embodiments, the individual fluids used for pretreatment may becontained in the system cabinet. Deparaffinization fluids (except DIwater) may be drawn into the processing tanks, then returned to theircontainers for reuse. Containers are as listed for fluids one throughsix. On a periodic basis, the material in the “dirty” containers may bediscarded. The “clean” containers may be moved up to the dirty position,and then fresh fluid added to clean position. DI water may be drawn fromthe large system DI water container, and discarded after each use.Target retrieval solution may be drawn from dedicated containers, andmay be recycled or discarded after each use.

In some embodiments, an imaging device such as an image-capture 2-Doptical sensor, perhaps a CCD camera, may be used to determine theposition of the sample on the slide, providing for greater accuracyduring sample processing. Embodiments of the sample processing system101 may further provide sample diagnostic capabilities. Accordingly, insome embodiments, a device may analyze samples. A camera may be used fordiagnostic purposes. In some embodiments, the sample may be scanned forfurther analysis, potentially by computer. The camera can also beused 1) as an area locator, 2) to locate a tissue area, 3) to applyreagent based on location and area. The scanned image may be analyzedfor reagent analysis or other analyses.

The processing of samples may be accomplished according to somepreferred embodiments as shown in FIG. 4 and consistent with features ofthe present invention. Variants of these protocols and processing steps,or other processing steps, may be accomplished consistent with thepresent invention.

One processing sequence may broadly comprise the pre-processing of asample, if needed, such as deparaffinization (as previously described),and further comprise target or epitope retrieval (as previouslydescribed), and sample staining.

In some embodiments, specifics of in-situ hybridization (ISH) may beaddressed. Embodiments of ISH may require a small volume of agent, suchas 15 microliters, to be placed on the sample. Heat control may bemaintained between about 95-100 C and kept constant for a period oftime. Temperature may then be lowered in a controlled manner.

Furthermore, fluorescent staining or tagging in IHC or ISH (FISH) may beperformed consistent with the features of the present invention.

As mentioned, the sample processing system may automate the processingof samples mounted on carriers or slides. This configuration of thesystem allows for the flexibility for both continuous, individual, andbatch processing of slides with the design lending itself to meetestablished laboratory workflow demands. The multiple independent andredundant slide processing subsystems found within the system may alsomaintain its ability to process each slide independently.

The automatic processing may be achieved by designing a system withautomated process operation capability or sequencing through at leastsome steps without human intervention that may be controlled by or actin response to a process operation control system 171. Of course, theuser needs the ability to specify the nature and sequence of the varioussteps or acts desired. This can be accomplished by an input parametercapability 173 through the inclusion of even a sample process parameterinput 173. This input can be retained by the creation of storedparameter process data 174. In order to facilitate uninterruptedprocessing, the input parameter capability 173 may be configured as anindependent process parameter input with respect to the processoperation control system 171, such that acts caused by the processoperation control system 171 are unaffected by any action with respectto the independent process parameter input. Further, the input parametercapability 173 may also be configured as an autonomous inputfunctionality through the inclusion of an autonomous input element. Inthis manner, the input parameter capability 173 may not only actindependent of the automated process operation capability, but it may befully functional even without the presence or operability of theautomated process operation capability (which itself may or may not bein a process device). This may be achieved in a variety of manners,including by providing a separate full function computer 181 (e.g.,separate from the capability provided or required by a process system)or that may be programmed to accomplish the input In addition, in orderto accomplish a goal of addressing practical and institutional needs,the input parameter capability 173 may be configured to provide asimplified entry parameter input functionality or as a simplified entryparameter input element. In this manner, only the input functions needto be available in a highly simplified level of detail. This may be a“wizard” type of system where there is a “step-by-step” method of addingslides or achieving the desired input. Such an aspect may even besimple, regimented, and somewhat inflexible. This can facilitate inputby persons not required to have the full spectrum of skills necessary tobe responsible for the operation of the sample processing system 101.

The input element such as hardware or software may be configured toaccept a variety of information, such as, but not limited to: inputtingat least some individual slide process information through inclusion ofan individual slide process-information input element, inputting atleast some group slide process information through inclusion of a groupslide process information input element, inputting at least some slideidentification information through inclusion of a slide identificationelement, inputting at least some preferred stainer information throughinclusion of a preferred stainer information input element, inputtinguser operation information through inclusion of a user information inputelement, inputting patient identification information through inclusionof a patient identification input element, inputting HIPPA-compliantidentification information through inclusion of a HIPPA-compliantidentification input element, inputting coded identification informationthrough inclusion of a coded identification input element, inputtinginternal identification information through inclusion of an internalidentification input element, inputting process protocol informationthrough inclusion of a process protocol information input element,inputting at least some process scheduling information through inclusionof a process scheduling information input element, inputting at leastsome process sequence information through inclusion of a processsequence information input element, inputting at least some processscheduler information through inclusion of a process schedulerinformation input element, inputting schedule priority informationthrough inclusion of a schedule priority information input element,inputting stat process request information through inclusion of a statprocess request input element, inputting at least some user or operatoridentification information through inclusion of a user id input elementor an operator id input element, inputting at least some user oroperator privileges information through inclusion of a user or operatorprivileges information input element, and batch processing parameterinput functionality through inclusion of a batch processing parameterinput element. Each of these types of elements may, of course, representhardware, software, a subroutine, or some combination thereof and may besimply the facilitation and perhaps even the simplification of the inputof the mentioned information. The inputs may also be configuredindependent from the automated process operation capability.

As used above, the slide identification information may represent anyinformation unique to a particular slide, such as a serial number,patient number, patient name, unique image, or the like. In keeping withprivacy concerns, there may also be coded identification information orinternal identification information that others cannot use to identifythe particular patient involved or the like. As discussed below and asshown in FIGS. 8 & 9, the overall system may include a number ofstainers and thus the input can include preferred stainer information(which may or may not be indicated or accepted by the automated system).Provision can also be included to achieve a rushed test and as suchthere may be a stat process request information element. Such may alsobe linked with a user privileges information so that only certainindividuals may displace other tests to create a different priority. Ofcourse all permutations and combinations of the above may be included.

For automated operation, the input may create data such as parameterprocess data 174 that may be stored at some location. To provideautonomous operation, it may be independently stored perhaps in aphysically independent memory even at a location remote from an actualstainer itself. This may be accomplished by utilizing a primary orsecondary storage perhaps of a separate full function computerprogrammed or configured to accept and/or store data. In such a fashion,the computer may contain what could be considered as an independentprocess parameter memory 174. Since the computer is likely physicallyseparate, it may be considered to have a physically independent memoryperhaps even a remote location memory if it is remote from the processequipment.

By using independent memory and independent other functionality, thesystem may facilitate full operational functionality of the automatedprocess operation capability. Since the automated process operationcapability is fully operational during operation of either the memory orinput, the storing or inputting or other function can be conductedwithout interrupting the process operation. Thus the inputs can be lateraccessed at a process time independent of the time of accomplishingslide process parameter input or storing. In addition, entry or storingmay also be accomplished at least in part concurrently with theprocessing of certain samples. This processing may even be initiatedsignificantly after completion of the slide process parameter inputaction. Such may occur at least about one hour after the input, at leastabout three hours after the input, at least about eight hours after theinput, at least about one day after the input, at least about two daysafter the input, and at least about one week after the input.

In some embodiments, the system may be comprised of independent orperhaps redundant slide staining modules (some embodiments may compriseeight modules) as shown for some embodiments in FIGS. 1 and 6.Throughput may be based on the time to first result with the systemallowing access to completed slides as soon as a staining module hascompleted the scheduled staining tasks. The multiple independent orredundant staining modules may allow for both continuous and batchprocessing of slides. Additionally, each independent staining module mayalso allow for the independent pre-treatment and staining of each slide.A carrier retainment assembly, such as a slide retainment assembly, maybe used to introduce slides to be processed into the drawer 104, thedrawer, slide retainment assembly, and components thereof forming astain module. The slides may occupy one or more positions of the slideretainment assembly, such as at carrier retention devices, up to thecapacity of the slide retainment assembly with the potential for eachslide being processed independently of other slides configured with theslide rack. Embodiments of the stain modules, drawers, slide racks, andcomponents thereof are also shown in FIG. 6. FIG. 6 also provides otherembodiments of system features, such as an embodiment of the arm 120 andthe component features of the arm.

Slide retainment assemblies having one or more slides may be introducedinto the staining modules by introduction into drawers 104 one at a timeor in any combination until all or an appropriate number of stainingmodules are appropriately occupied. There may be no restrictions as tothe order, number or timing of when the slide retainment assemblies areintroduced into the system, the system may also allow for adaptivescheduling of sample loading. Staining modules, and in some embodimentsthe drawers of the staining modules, may lock out access to the slidesduring the processing period and may release them to the operator uponcompletion of the staining or other process on the last slide of thatmodule. In some embodiments, the order in which the slide retainmentassemblies are released may be dependant on the time required to processthe last slide of the retainment assembly. Slides may even be processedin the most time efficient manner independently of the order to whichthey were introduced into the system. The system may provide an optimumor merely an enhanced temporal scheduling of the various sample processsteps. To accomplish this, the system may automatically schedule stepsthat are interspersed for an enhanced time result. This interspersingmay be an interleaving of a number of process operations and even aninterleaving of a number of individual sample operations. In addition tointerleaving steps, the system may sequence the individual sampleoperations. Regardless as to how programmed, it may be configuredthrough hardware or software or a combination of each to provide anenhanced temporal scheduler element 179, a process operations interleaveelement, an individual sample operations interleave element, or even anindividual sample operations sequence element. These can be created byintegrating the automated process operation capability and either theparameter data or perhaps some replicated portion of that parameterprocess data (as mentioned later) and can thus act to create aninterspersial robotic control functionality 175.

The control of the processing samples may be accomplished according tothe following preferred embodiments, one preferred embodiment shown inFIG. 5, although other processing may be accomplished consistent withthe present invention.

As shown in FIGS. 8 & 9, in expanded systems, a sample processing systemmanager, such as a computer server may be connected with a number ofindividual sample processing systems. These may represent automatedslide stainers or even stand alone automated slide processing systemsuch that they are fully capable of functioning with connection to otherdevices. In systems where a connection does exist, the capability ofelectronically connecting a number of automated slide stainers orautomated sample processing systems or label printers 200 may beprovided. As mentioned earlier, there may be one or more separate fullfunction computers connected. These may be connected through a hub 193.There may be a multitasked central processing unit resource on eitherthe stainer or the computer or there may be a number of centralprocessing units that are configured to avoid using or implementing amultitasked central processing unit resource relative to the processoperations in order to maintain full independence or perhaps evenautonomous operation. The connection, whether for input or otheroperation may also be a remote link (including able to be made remotesuch as in detachable memory) such as an internet connection element, atelephone line connection element, a wireless communication element, oreven a detachable memory element. In a preferred embodiment, connectionamong perhaps a number of process systems and perhaps a number ofcomputers, such as workstations and a server (the latter residing eitherseparately or as part of a workstation), may be achieved by use of alocal area network, such as a group of computers and associated devicesthat share a common communications line or perhaps wireless link and mayeven share the resources of a single processor, memory, or server withina small geographic area (for example, within an office building orcomplex). A local area network for this type of system may also includefeatures such as but not limited to: an Ethernet element, a token ringelement, an arcnet element, a fiber distributed data interface element,an industry specification protocol, a bluetooth-based element (named butnot contemporary to King Harald Bluetooth of Denmark in the mid-tenthcentury!), a telecommunications industry specification using a frequencyband of 2.45 GHz, a communication specification applying an IEEE 802standard, a frequency hop communication specification, a shared commonlink element, a transmission control protocol/internet protocolcommunication element, a packetized information protocol, a sharedprotocol, a proprietary protocol, and even a layered protocol exchangesystem. By providing an electronic connection 176 between variousresources, the local area network (LAN) such as the stainer network 183(a network dedicated to only the stainer or perhaps sample processingresources for integrity, security, and other purposes) in one embodimentmay transmit a electronic memory address to achieve access to theappropriate information. Connection may also be established to a labnetwork or even a lab information system 195 such as through a bridge194.

As mentioned, connection may be accomplished over internet connectionsbut more preferably is accomplished over LAN connections. Each sampleprocessing system may be individually controlled, in some embodiments,by a PC attached with, internal to, or otherwise provided. Data sharingbetween sample processing systems and the system manager may beperformed to allow identification, tracking, and status of samplebatches, reagents, and other agents and components of the sampleprocessing system. A determination of which system has which reagents,reagent type, slides and protocols may be performed. Log files for eachprocessing sequence, protocol, or slide can be generated for monitoringprocessing status. Database maintenance (including but not limited topurge, compact, back-up, database/list functions) and system diagnostics(including but not limited to exercising active system components toverify proper operation and assisting in troubleshooting efforts) may beaccomplished manually or automatically.

The system may be configured to automatically access the required datathrough operation of the process operation control system 171 byinclusion of an automatic memory access element. This access may beachieved by specifying an electronic memory address that may betransmitted by a electronic memory address element 178 perhaps over alocal area network and may be followed by automatically replicating thatdata on some a memory aspect appropriate for operation such as anautomatic data replication memory. This memory may include but not belimited to: a volatile memory functionality as implemented by a volatilememory element, a random access memory functionality as implemented by arandom access memory element, a non-volatile memory functionality asimplemented by a non-volatile memory element, an electrically erasableprogrammable read only memory functionality as implemented by anelectrically erasable programmable read only memory element, a mainstorage functionality as implemented by a main storage element, asecondary storage functionality as implemented by a secondary storageelement, a cache memory functionality as implemented by a cache memoryelement, and even a detachable memory functionality as implemented by adetachable memory element.

A control interface may be provided for the operator, such as agraphical user interface (GUI), and may accommodate various languages.Help menus may be provided to assist in sample processing. Passwordprotection features can be provided and even administrator control overat least some aspects. This may include the capability to includeadministrator limitations on the functional availability of any aspectof the system or of specific stainer availability or functionality,certain reagent availability functionality, certain protocolavailability functionality, patient identification information accessfunctionality, process priority request functionality, and stat processrequest functionality. By including an administrator control element180, the system may have an administrator-implemented user limitationelement, a specific stainer availability limitation element, a certainreagent availability limitation element, a certain protocol availabilitylimitation element, a patient identification information accesslimitation element, a process priority request limitation element, astat process request limitation element, a user privileges inputelement, and even a user group privileges configuration or inputelement.

Control of the sample processing may be accomplished by a dynamicscheduling algorithm, and in some embodiments, in accordance withcontinuous, or batch processing previously described. The processingsequence may be controlled, in preferred embodiments, such that thevarious steps of a protocol for samples may be automated by one or morealgorithmic controls. As part of input to establish the desired controlfunctionality, user or other input may be accommodated as follows: 1)selecting a first protocol step, 2) selecting a second protocol from arestricted list of menu items that are compatible with the firstprotocol step, and 3) selecting subsequent protocol steps from arestricted list of menu items that are compatible with the precedingprotocol step.

After all data is input, the system may act to determine operationalreadiness by inclusion of an operational readiness determination element177 that may be programmed to assess if appropriate resources, drawers,slides, reagents, or other aspects are present or available to thesystem. Once an appropriate operational readiness is determined, thesystem may prompt initiation of access of the input data toelectronically determine operational availability of a variety of items.These may include but are not limited to: an individual sample elementthrough inclusion of an individual sample readiness determinationelement, a defined group of samples through inclusion of a defined groupof samples readiness determination element, a physically groupedcollection of samples through inclusion of a physically groupedcollection of samples readiness determination element, a slide drawercomponent through inclusion of a slide drawer component readinessdetermination element, a stand alone automated slide processing systemthrough inclusion of an stand alone automated slide processing systemreadiness determination element, a slide stainer system element throughinclusion of a slide stainer system readiness determination element, andeven a user initiated prompt signal such as might occur to force oractivate the system manually by the inclusion of a user initiated promptsignal determination element.

One aspect of the invention focuses on an automated staining apparatusand a method of automated treating of samples. As to this aspect, thepresent invention relates to an automated staining apparatus fortreating samples arranged on carrier elements or means, such as but notlimited to microscope slides, located at defined positions close to orin the apparatus by removing a portion of selected reagent from astation containing a plurality of reagents and thereafter applying thereagent to a sample, e.g. a tissue, organic cells, bacteria etc.,arranged on the carrier means. This aspect of the invention facilitatesthat two or more reagents are mixed and the mixture applied to a sample.It also relates to a method of automated treating of samples by mixingreagents and applying the mixture to the sample.

Staining apparatuses for staining and treating samples by means ofprobes normally comprises a first station for containing one or morereagent vials; a second station for mounting slides, a probe arrangedfor removing a portion of reagent from a selected reagent vial andapplying the reagent to a slide on which the sample is arranged and adrive means for moving the probe between the various stations.

An object of this aspect of the present invention is to improve theknown apparatuses for staining samples as well as the method forautomatic staining of samples by facilitating a wider range of availableprocesses or procedures used to implement treatment, so as to ease theimplementation of different staining and/or treatment processes that maybe performed automatically, alternatively or additionally to provide anincreased quality of some specific staining processes.

The term staining is used for the end product of the process, by whichcertain parts of the sample may be stained, i.e. has obtained adifferent colour, either in the optic range or in anotherelectromagnetic range, such as ultra violet, or the staining may be andetectable, preferably automatically detectable, change in properties,such as fluorescent properties, magnetic properties, electricalproperties or radioactive properties. To obtain the staining, the samplenormally has to undergo a series of treatment steps, such as washing,binding of reagents to the specific parts of the sample, activation ofthe reagents, etc. and each treatment step may include a plurality ofindividual treatments.

In some staining processes, it may be required for one or moretreatments to use a mixture of reagents prepared from two or moreseparate reagents which may be somewhat incompatible e.g. unmixable,such as a water based and an oil based reagent, or insoluble, andtherefore requires that the two or more reagents are manually preparedand introduced into a reagent vial shortly before starting the stainingprocess in order to obtain the best possible staining result for theselected examination purposes. For other processes, different stainingprocess steps require a mixture of the same two reagents but indifferent dissolution ratios. Some process steps require mixtures of twoor more reagents that, when mixed, have a limited time window ofusability because internal chemical processes deteriorate the mixture.By providing a staining apparatus having an automated mixer integratedtherein, these types of staining processes can be performedautomatically instead of requiring human interaction or manualperformance of some process steps in a much more automated process, andthe quality of the staining process may be improved as a desired degreeof mixing of reagents may be provided or an optimal application timewindow for a deteriorating mixture may be reached.

The carrier elements or perhaps means are preferably arranged in groupsor series on trays or the like, so that a plurality of carrier means maybe removed from or situated in the apparatus simultaneously, and theapparatus preferably also comprises means for performing theintermediate storage of the carrier means with samples thereon and theremoval of the carrier means from the apparatus automatically.

The operation of the staining apparatus will generally be controlled bymeans of control means, typically a computer having a central processingunit and one or more memory unit associated therewith, means forcontrolling the various operations of the apparatus by controlling stepmotors, solenoids, valves and/or other drive or control parts of theapparatus. The control means may have one or more data communicationports for enabling data communication with external computers by wire orwireless elements. The control element or perhaps means does not have tobe physically arranged within the apparatus itself but may be a computerexternal to the staining apparatus and connected to the apparatus via adata transmission port thereof.

The present invention also relates to a method of fully automatedtreating of samples arranged on carrier elements by means of a stainingapparatus controlled by means of a control element or means, wherein themethod comprises the steps of situating a plurality of carrier meansintermediately in a carrier means station, each carrier means having asample arranged thereon, applying a portion of a first reagent selectedfrom a plurality of reagents to a mixing cup, applying a portion of asecond reagent selected from a plurality of reagents to the mixing cup,mixing the reagents in the mixing cup by means of mixing means, moving aprobe to the mixing cup by means of a probe drive means, removing aportion of the mixed reagents from the mixing cup by means of the probe,moving the probe to a selected one of said carrier means, and applyingthe mixed reagents to the selected carrier means, so as to perform atreatment of the sample arranged on the selected carrier means.

The present invention further relates to the use of an apparatus of thepresent invention as described above for exercising the method of thepresent invention.

The embodiment shown in the figures and described in details below isonly an example of an apparatus in accordance with the present inventionand is not limiting the wider scope of the invention as described in theenclosed claims.

As shown in FIG. 6, a detailed description of one embodiment of thisaspect of the invention involves staining apparatus 201; The stainingapparatus 201 may comprise a rectangular frame 204 surrounding a firststation 202 comprising an array of compartments wherein each compartmenta reagent vial 203 is placed, and a second station 205 wherein a numberof separate racks 206 is placed, and where each rack may comprise anumber of microscope slides 207 mounted side by side in the rack 206. Inthe embodiment shown, each rack may hold up to 17 slides, but the rackmay be designed to hold any suitable number of slides. With eight racksarranged side by side; the shown embodiments may hold up to 136 slides207 each having a sample, e.g. a tissue mounted on the upper side of theslide, so that reagent may be applied from above to the sample on eachslide.

A robot arm to move a probe 210 in X and Y direction as indicated by thearrows X and Y may be arranged above the frame 204 of the stainingapparatus. The robot arm may therefore position the probe 210 above allreagent vials 203 as well as above all the microscope slides 207, andmay further operate the probe 210 to remove portions of a reagentcontained in any of the vials or containers 203, to transfer the portionof reagent and apply it to any of the slides 207 in order to provide aselected staining or treatment of the sample on each slide 207. By useof a suitable control element, e.g. a computer having the appropriatesoftware, subroutines, or input data for the purpose, this stainingapparatus 201 may be able to automatically stain or treat samplesrequiring different staining or treatment reagents and processes.

Having the appropriate input data, the control element or perhaps meansof the apparatus may operate the robot arm to commence a staining ortreatment run by firstly moving the probe to a first reagent vial orcontainer 203, into which the probe tip is inserted and liquid isaspirated up into the probe 210 in an amount corresponding to the numberof samples to be stained or treated, in accordance with the input dataprovided to the control element. Additionally, under certain conditions,the instrument may be required to perform a reagent inventory before astaining or treatment run can commence. This inventory may beaccomplished by use of the probe tip to actually touch the liquidsurface in each reagent vial 203. To prevent cross-contamination betweenthe reagents in the various vials 203, a cleaning of the probe 210 or atleast the probe tip may be required after each measurement of a reagentlevel.

The probe 210 may be moved by the robot arm towards the slide racksystem 205 in which the slides 207 are mounted. The slides 207 may besituated with the surface horizontally oriented and the probe 124 maydispense the required amount of reagent on the appropriate slides inaccordance with the input data. Alternatively, the probe 124 may bemoved by the robot arm towards the reagent mixer 209 where it mayrelease reagent into the cup of the reagent mixer 209, and may besubsequently moved to the probe washing station 208, where the probe 210may be released into a free washing station 208, and another probesituated in another washing station 208 may be connected to the robotarm. The robot arm may move the new clean probe to a second selectedreagent vial 203 for collecting a selected amount of reagent from thesecond vial 203, and the probe may thereafter by means of the robot armbe moved to the reagent mixer 209, where the reagent in the probe 210may be released into the cup of the mixer containing the first selectedreagent. This may be commenced several times if more than two reagentsare to be mixed for a specific staining or treatment process.

An object of the present invention is to provide a staining apparatusand a method for automatic staining of samples, in which the totalprocess time for completing or even entering the staining protocol maybe reduced. In particular, it is an object of this aspect of theinvention to reduce the amount of time needed in general.

As can be easily understood from the foregoing, the basic concepts ofthe present invention may be embodied in a variety of ways. It involvesboth sample processing techniques as well as various systems,assemblies, and devices to accomplish sample processing, input, andother functions. In this application, the sample processing techniquesare also disclosed as part of the results shown to be achieved by thevarious systems, assemblies, and devices described and as steps whichare inherent to utilization. They should be understood to be the naturalresult of utilizing the devices as intended and described. In addition,while some devices are disclosed, it should be understood that these notonly accomplish certain methods but also can be varied in a number ofways. Importantly, as to all of the foregoing, all of these facetsshould be understood to be encompassed by this disclosure.

The discussion included in this application is intended to serve as abasic description. The reader should be aware that the specificdiscussion may not explicitly describe all embodiments possible; manyalternatives are implicit. It also may not fully explain the genericnature of the invention and may not explicitly show how each feature orelement can actually be representative of a broader function or of agreat variety of alternative or equivalent elements. Again, these areimplicitly included in this disclosure. Where the invention is describedin device-oriented terminology, each element of the device implicitlyperforms a function. Importantly, neither the description nor theterminology is intended to limit the scope of the claims which may beincluded at any time.

It should also be understood that a variety of changes may be madewithout departing from the essence of the invention. Such changes arealso implicitly included in the description. They still fall within thescope of this invention. A broad disclosure encompassing both theexplicit embodiment(s) shown, the great variety of implicit alternativeembodiments, and the broad methods or processes and the like areencompassed by this disclosure and may be relied upon at any time.

Further, each of the various elements of the invention and claims mayalso be achieved in a variety of manners. This disclosure should beunderstood to encompass each such variation, be it a variation of anembodiment of any apparatus embodiment, a method or process embodiment,or even merely a variation of any element of these. Particularly, itshould be understood that as the disclosure relates to elements of theinvention, the words for each element may be expressed by equivalentapparatus terms or method terms—even if only the function or result isthe same. Such equivalent, broader, or even more generic terms should beconsidered to be encompassed in the description of each element oraction. Such terms can be substituted where desired to make explicit theimplicitly broad coverage to which this invention is entitled. As butone example, it should be understood that all actions may be expressedas a means for taking that action or as an element which causes thataction. Similarly, each physical element disclosed should be understoodto encompass a disclosure of the action which that physical elementfacilitates. Regarding this last aspect, as but one example, thedisclosure of a “retention element” should be understood to encompassdisclosure of the act of “retaining”—whether explicitly discussed ornot—and, conversely, were there effectively disclosure of the act of“retaining”, such a disclosure should be understood to encompassdisclosure of a “retention element” and even a “means for retaining”. Itshould also be understood that in jurisdictions where specific languagemay be construed as limiting, as but one example in the United Stateswhere some interpretations of “means for” elements can be construednarrowly, broader equivalent language may be used and should beunderstood as encompassed by this specification. Such changes andalternative terms are to be understood to be explicitly included in thedescription.

Any patents, patent applications, publications, or other referencesmentioned in this application for patent are hereby incorporated byreference. In addition, as to each term used it should be understoodthat unless its utilization in this application is inconsistent withsuch interpretation, common dictionary definitions should be understoodas incorporated for each term and all definitions, alternative terms,and synonyms such as contained in the Random House Webster's UnabridgedDictionary, second edition are hereby incorporated by reference as wellas the definitions presented by searchstorage.com, such to be consideredas representing the meaning of the terms as understood by computerprofessionals. Finally, any priority case for this application is herebyappended and hereby incorporated by reference.

Thus, the applicant(s) should be understood to have support to claim atleast: i) each of the sample processing systems and subsystems as hereindisclosed and described, ii) the related methods disclosed anddescribed, iii) similar, equivalent, and even implicit variations ofeach of these systems, assemblies, devices and methods, iv) thosealternative designs which accomplish each of the functions shown as aredisclosed and described, v) those alternative designs and methods whichaccomplish each of the functions shown as are implicit to accomplishthat which is disclosed and described, vi) each feature, component, andstep shown as separate and independent inventions, vii) the applicationsenhanced by the various systems or components disclosed, viii) theresulting products produced by such systems or components, and ix)methods and systems, assemblies, devices, and apparatuses substantiallyas described hereinbefore and with reference to any of the accompanyingexamples, x) the various combinations and permutations of each of theelements disclosed, xi) each potentially dependent claim or concept as adependency on each and every one of the independent claims or conceptspresented, xii) processes performed with the aid of or on a computer asdescribed throughout the above discussion, xiii) a programmable systemas described throughout the above discussion, xiv) a computer readablememory encoded with data to direct a computer comprising means orelements which function as described throughout the above discussion,xv) a computer configured as herein disclosed and described, xvi)individual or combined subroutines and programs as herein disclosed anddescribed, xvii) the related methods disclosed and described, xviii)similar, equivalent, and even implicit variations of each of thesesystems and methods, xix) those alternative designs which accomplisheach of the functions shown as are disclosed and described, xx) thosealternative designs and methods which accomplish each of the functionsshown as are implicit to accomplish that which is disclosed anddescribed, xxi) each feature, component, and step shown as separate andindependent inventions, and xxii) the various combinations andpermutations of each of the above.

Further, if or when used, the use of the transitional phrase“comprising” or the like is used to maintain the “open-end” claimsherein, according to traditional claim interpretation. Thus, unless thecontext requires otherwise, it should be understood that the term“comprise” or variations such as “comprises” or “comprising” or thelike, are intended to imply the inclusion of a stated element or step orgroup of elements or steps but not the exclusion of any other element orstep or group of elements or steps. Such terms should be interpreted intheir most expansive form so as to afford the applicant the broadestcoverage legally permissible.

Any claims set forth at any time are hereby incorporated by reference aspart of this description of the invention, and the applicant expresslyreserves the right to use all of or a portion of such incorporatedcontent of such claims as additional description to support any of orall of the claims or any element or component thereof, and the applicantfurther expressly reserves the right to move any portion of or all ofthe incorporated content of such claims or any element or componentthereof from the description into the claims or vice-versa as necessaryto define the matter for which protection is sought by this applicationor by any subsequent continuation, division, or continuation-in-partapplication thereof, or to obtain any benefit of, reduction in feespursuant to, or to comply with the patent laws, rules, or regulations ofany country or treaty, and such content incorporated by reference shallsurvive during the entire pendency of this application including anysubsequent continuation, division, or continuation-in-part applicationthereof or any reissue or extension thereon.

1. A method of automated sample processing comprising the steps of:establishing an automated sample processing system having an automatedprocess operation capability to which robotic sample process functionsare responsive; providing an input parameter capability independent ofsaid automated process operation capability; accomplishing sampleprocess parameter input to said input parameter capability withoutinterrupting said automated process operation capability; independentlystoring at least a portion of said parameter input for later access;establishing stored parameter process data; automatically accessing atleast a portion of said stored parameter process data through operationof said automated process operation capability; automaticallyreplicating at least a portion of said stored parameter process data foruse by said automated process operation capability; integrating saidautomated process operation capability and said replicated portion ofsaid stored parameter process data to create an interspersial roboticcontrol functionality; controlling at least some of said robotic sampleprocess functions in response to said interspersial robotic controlfunctionality; and automatically processing at least one sample throughoperation of said robotic sample process functions at a process timeindependent of the time said step of accomplishing slide processparameter input to said input parameter capability without interruptingsaid automated process operation capability is accomplished.
 2. A methodof automated sample processing as described in claim 1 wherein said stepof establishing an automated sample processing system having anautomated process operation capability to which robotic sample processfunctions are responsive comprises the step of establishing an automatedslide processing system.
 3. A method of automated sample processing asdescribed in claim 2 wherein said step of automatically processing atleast one sample comprises the steps of: arranging a plurality of slideson a carrier retainment assembly; applying a reagent to said pluralityof slides; and automatically staining said plurality of slides.
 4. Amethod of automated sample processing as described in claim 3 whereinsaid step of establishing an automated sample processing system havingan automated process operation capability to which robotic sampleprocess functions are responsive comprises the steps of: establishing aplurality of automated slide stainers; and electronically connectingsaid plurality of automated slide stainers.
 5. A method of automatedsample processing as described in claim 1 wherein said step ofestablishing an automated sample processing system comprises the step ofestablishing a stand alone automated slide processing system, andwherein said step of providing an input parameter capability independentof said automated process operation capability comprises the steps of:utilizing a separate full function computer programmed to accomplishsaid input; and electronically connecting said separate full functioncomputer to said stand alone automated slide processing system.
 6. Amethod of automated sample processing as described in claim 1 andfurther comprising the step of establishing a local area networkelectronically connected to said automated sample processing system. 7.A method of automated sample processing as described in claim 6 whereinsaid step of establishing a local area network electronically connectedto said automated sample processing system comprises the step ofincorporating a system having a feature selected from a group consistingof: an Ethernet element, a token ring element, an arcnet element, afiber distributed data interface element, an industry specificationprotocol, a bluetooth-based element, a shared common link element, atransmission control protocol/internet protocol communication element, apacketized information protocol, a shared protocol, a proprietaryprotocol, and a layered protocol exchange system.
 8. A method ofautomated sample processing as described in claim 3 and furthercomprising the step of holding said plurality of slides on at least onemovable carrier retainment assembly.
 9. A method of automated sampleprocessing as described in claim 8 and further comprising the step ofautomatically identifying said plurality of slides.
 10. A method ofautomated sample processing as described in claim 1 wherein said step ofproviding an input parameter capability independent of said automatedprocess operation capability comprises the step of providing anautonomous input functionality.
 11. A method of automated sampleprocessing as described in claim 1 wherein said step of providing aninput parameter capability independent of said automated processoperation capability comprises the step of utilizing a multitaskedcentral processing unit resource.
 12. A method of automated sampleprocessing as described in claim 1 wherein said step of providing aninput parameter capability independent of said automated processoperation capability comprises the step of utilizing a plurality ofcentral processing units without implementing a multitasked centralprocessing unit resource.
 13. A method of automated sample processing asdescribed in claim 1 and further comprising the step of providing fulloperational functionality of said automated process operation capabilitywhile accomplishing said sample process parameter input.
 14. A method ofautomated sample processing as described in claim 1 wherein said step ofproviding an input parameter capability independent of said automatedprocess operation capability comprises the step of utilizing a remotelink to said automated sample processing system.
 15. A method ofautomated sample processing as described in claim 10 wherein said stepof establishing an automated sample processing system having anautomated process operation capability to which robotic sample processfunctions are responsive comprises the steps of: establishing aplurality of automated slide stainers; and electronically connectingsaid plurality of automated slide stainers.
 16. A method of automatedsample processing as described in claim 10 wherein said step ofestablishing an automated sample processing system comprises the step ofestablishing a stand alone automated slide processing system, andwherein said step of providing an input parameter capability independentof said automated process operation capability comprises the steps of:utilizing a separate full function computer programmed to accomplishsaid input; and electronically connecting said separate full functioncomputer to said stand alone automated slide processing system.
 17. Amethod of automated sample processing as described in claim 10 andfurther comprising the step of establishing a local area networkelectronically connected to said automated sample processing system. 18.A method of automated sample processing as described in claim 17 whereinsaid step of establishing a local area network electronically connectedto said automated sample processing system comprises the step ofincorporating a system having a feature selected from a group consistingof: an Ethernet element, a token ring element, an arcnet element, afiber distributed data interface element, an industry specificationprotocol, a bluetooth-based element, a shared common link element, atransmission control protocol/internet protocol communication element, apacketized information protocol, a shared protocol, a proprietaryprotocol, and a layered protocol exchange system.
 19. A method ofautomated sample processing as described in claim 14 wherein said stepof utilizing a remote link to said automated sample processing systemcomprises the step of utilizing a remote link having a feature selectedfrom a group consisting of: an internet connection element, a telephoneline connection element, a wireless communication element, and adetachable memory element.
 20. A method of automated sample processingas described in claim 1 wherein said step of providing an inputparameter capability independent of said automated process operationcapability comprises the step of utilizing a simplified entry parameterinput functionality.
 21. A method of automated sample processing asdescribed in claim 1 wherein said step of providing an input parametercapability independent of said automated process operation capabilitycomprises the step of utilizing a batch processing parameter inputfunctionality.
 22. A method of automated sample processing as describedin claim 1 wherein at least a portion of said step of automaticallyprocessing occurs at least in part concurrently with at least a portionof said step of accomplishing slide process parameter input.
 23. Amethod of automated sample processing as described in claim 1 whereinthe initiation of said step of automatically processing for certainsamples occurs significantly after completion of said step ofaccomplishing slide process parameter input for said certain samples.24. A method of automated sample processing as described in claim 23wherein said step of automatically processing for certain samples isinitiated at a time after the completion of said step of accomplishingslide process parameter input for said certain samples, said timeselected from a group consisting of: at least about one hour, at leastabout three hours, at least about eight hours, at least about one day,at least about two days, and at least about one week.
 25. A method ofautomated sample processing as described in claim 1 wherein said step ofaccomplishing sample process parameter input to said input parametercapability without interrupting said automated process operationcapability comprises the step of utilizing an autonomous inputfunctionality.
 26. A method of automated sample processing as describedin claim 1 wherein said step of accomplishing sample process parameterinput to said input parameter capability without interrupting saidautomated process operation capability comprises the step of utilizing amultitasked central processing unit resource.
 27. A method of automatedsample processing as described in claim 1 wherein said step ofaccomplishing sample process parameter input to said input parametercapability without interrupting said automated process operationcapability comprises the step of utilizing a plurality of centralprocessing units without implementing a multitasked central processingunit resource.
 28. A method of automated sample processing as describedin claim 1 wherein said step of accomplishing sample process parameterinput to said input parameter capability without interrupting saidautomated process operation capability comprises the step of inputtingat least some slide identification information.
 29. A method ofautomated sample processing as described in claim 28 wherein said stepof inputting at least some slide identification information comprisesthe step of inputting information selected from a group consisting of:user operation information, patient identification information,HIPPA-compliant identification information, coded identificationinformation, and internal identification information.
 30. A method ofautomated sample processing as described in claim 1 wherein said step ofaccomplishing sample process parameter input to said input parametercapability without interrupting said automated process operationcapability comprises the step of inputting at least some processscheduling information.
 31. A method of automated sample processing asdescribed in claim 1 wherein said step of accomplishing sample processparameter input to said input parameter capability without interruptingsaid automated process operation capability comprises the step ofinputting at least some process sequence information.
 32. A method ofautomated sample processing as described in claim 31 wherein said stepof inputting at least some process sequence information comprises thestep of inputting at least some schedule priority information.
 33. Amethod of automated sample processing as described in claim 31 whereinsaid step of inputting at least some process sequence informationcomprises the step of inputting at least some stat process requestinformation.
 34. A method of automated sample processing as described inclaim 1 wherein said step of accomplishing sample process parameterinput to said input parameter capability without interrupting saidautomated process operation capability comprises the step of inputtingat least some process protocol information.
 35. A method of automatedsample processing as described in claim 1 and further comprising thestep of providing for administrator control over at least some aspectsof said automated sample processing system.
 36. A method of automatedsample processing as described in claim 35 wherein said step ofproviding for administrator control over at least some aspects of saidautomated sample processing system comprises the step of permittingadministrator limitations on the functional availability of at leastsome functionality of said automated sample processing system.
 37. Amethod of automated sample processing as described in claim 36 whereinsaid step of permitting administrator limitations on the functionalavailability of at least some functions of said automated sampleprocessing system comprises the step of permitting administratorlimitations on automated sample processing system functionality selectedfrom a group consisting of: specific stainer availability functionality,certain reagent availability functionality, certain protocolavailability functionality, patient identification information accessfunctionality, process priority request functionality, and stat processrequest functionality.
 38. A method of automated sample processing asdescribed in claim 1 wherein said step of accomplishing sample processparameter input to said input parameter capability without interruptingsaid automated process operation capability comprises the step ofinputting at least some user privileges information.
 39. A method ofautomated sample processing as described in claim 1 wherein said step ofaccomplishing sample process parameter input to said input parametercapability without interrupting said automated process operationcapability comprises the step of inputting at least some individualslide process information.
 40. A method of automated sample processingas described in claim 1 wherein said step of accomplishing sampleprocess parameter input to said input parameter capability withoutinterrupting said automated process operation capability comprises thestep of inputting at least some group slide process information.
 41. Amethod of automated sample processing as described in claim 1 whereinsaid step of accomplishing sample process parameter input to said inputparameter capability without interrupting said automated processoperation capability comprises the step of inputting at least somepreferred stainer information.
 42. A method of automated sampleprocessing as described in claim 1 wherein said step of independentlystoring at least a portion of said parameter input for later accesscomprises the step of storing at least a portion of said parameter inputon a physically independent memory.
 43. A method of automated sampleprocessing as described in claim 1 wherein said step of storing at leasta portion of said parameter input on a physically independent memorycomprises the step of storing at least a portion of said parameter inputat a location remote from said automated sample processing system.
 44. Amethod of automated sample processing as described in claim 42 whereinsaid step of storing at least a portion of said parameter input on aphysically independent memory comprises the steps of: utilizing aseparate full function computer programmed to accept and store at leasta portion of said parameter input; and electronically connecting saidseparate full function computer to a stand alone automated slideprocessing system.
 45. A method of automated sample processing asdescribed in claim 44 wherein said step of automatically accessing atleast a portion of said stored parameter process data through operationof said automated process operation capability comprises the step ofspecifying an electronic memory address for at least a portion of saidstored parameter process data.
 46. A method of automated sampleprocessing as described in claim 45 wherein said step of automaticallyaccessing at least a portion of said stored parameter process datathrough operation of said automated process operation capability furthercomprises the step of transmitting said electronic memory address over alocal area network electronically connected to said automated sampleprocessing system.
 47. A method of automated sample processing asdescribed in claim 1 wherein said step of automatically accessing atleast a portion of said stored parameter process data through operationof said automated process operation capability comprises the step ofutilizing a remote link to said automated sample processing system. 48.A method of automated sample processing as described in claim 47 whereinsaid step of utilizing a remote link to said automated sample processingsystem comprises the step of utilizing a remote link having a featureselected from a group consisting of: an internet connection element, atelephone line connection element, a wireless communication element, anda detachable memory element.
 49. A method of automated sample processingas described in claim 1 wherein said step of automatically accessing atleast a portion of said stored parameter process data through operationof said automated process operation capability comprises the steps of:determining operational readiness of at least a portion of saidautomated sample processing system functionality; and promptinginitiation of access of at least a portion of said stored parameterprocess data in response to said step of determining operationalreadiness of at least a portion of said automated sample processingsystem functionality.
 50. A method of automated sample processing asdescribed in claim 49 wherein said step of determining operationalreadiness of at least a portion of said automated sample processingsystem functionality comprises the step of electronically determiningoperational availability of an automated sample processing system aspectselected from a group consisting of: an individual sample element, adefined group of samples, a physically grouped collection of samples, aslide drawer component, an stand alone automated slide processingsystem, a slide stainer system element, and a user initiated promptsignal.
 51. A method of automated sample processing as described inclaim 1 wherein said step of automatically replicating at least aportion of said stored parameter process data for use by said automatedprocess operation capability comprises the step of automaticallyreplicating on a memory aspect selected from a group consisting of: avolatile memory functionality, a random access memory functionality, anon-volatile memory functionality, an electrically erasable programmableread only memory functionality, a main storage functionality, asecondary storage functionality, a cache memory functionality, and adetachable memory element.
 52. A method of automated sample processingas described in claim 1 wherein said step of integrating said automatedprocess operation capability and said replicated portion of said storedparameter process data to create an interspersial robotic controlfunctionality comprises the step of accomplishing enhanced temporalscheduling of a plurality of sample process steps.
 53. A method ofautomated sample processing as described in claim 52 wherein said stepof integrating said automated process operation capability and saidreplicated portion of said stored parameter process data to create aninterspersial robotic control functionality comprises the step ofinterleaving a plurality of process operations.
 54. A method ofautomated sample processing as described in claim 1 wherein said step ofintegrating said automated process operation capability and saidreplicated portion of said stored parameter process data to create aninterspersial robotic control functionality comprises the step ofinterleaving a plurality of individual sample operations.
 55. A methodof automated sample processing as described in claim 1 wherein said stepof integrating said automated process operation capability and saidreplicated portion of said stored parameter process data to create aninterspersial robotic control functionality comprises the step ofsequencing a plurality of individual sample operations.
 56. An automatedsample processing system comprising: at least one sample arranged on acarrier element; a process operation control system configured to atleast partially process said sample; robotic motion system responsive tosaid process operation control system; an independent process parameterinput configured independent from said process operation control system;an independent process parameter memory responsive to said processparameter input configured to store at least some parameter processdata; an automatic memory access element; an automatic data replicationmemory responsive to said automatic memory access element and at least aportion of said parameter process data; and an interspersial roboticcontrol element responsive to said automatic data replication memory andto which said robotic motion system is responsive. 57-104. (canceled)